Cocaine-amphetamine regulated transcript (CART) neuropeptides appear to be involved in the brain's reward/reinforcement circuit. For instance, CART peptides have psychostimulant-like effects and may be involved in-the rewarding actions of cocaine, amphetamine, and other psychostimulants. The expression of CART mRNA and peptide is strictly regulated. Therefore, the major focus of the current proposal is to characterize the regulation of CART expression in-vivo in the rat NAc. The hypothesis under investigation is that CART mRNA and peptide expression are regulated via cAMP/PKA/CREB signaling. Experiments are designed to determine, 1) if forskolin injection into the NAc increases CART mRNA and peptide expression, 2) if forskolin's effects on CART expression are mediated through PKA, 3) if manipulating CART gene levels with viral vectors effects the expression of CART mRNA and peptides. By identifying and characterizing the signaling mechanism(s) responsible for regulating expression of CART mRNA and peptide, this project will contribute to the understanding of the brain's reward circuitry and the CART peptide, which may potentially serve as a therapeutic target for treatment of cocaine or psychostimulant abuse and addiction.